Due to the established link between tissue function, metabolism, and tissue perfusion, magnetic resonance (MR) hemodynamic imaging can offer a unique window into the function of the normal and pathophysiologically altered brain. The overall goal of this revised renewal is to develop and validate MR imaging techniques based on susceptibility contrast that are optimally sensitive in detecting and characterizing regional brain microscopic hemodynamics by using kinetic modeling of injected contrast agents. Our focus is on the accurate measurement of cerebral blood volume (CBV) and cerebral blood flow (CBF); our preliminary data suggest that both can be imaged with high spatial and temporal resolution. Along with conventional techniques, we plan to use high speed "single shot" or echo planar imaging (EPI) techniques, which provide the necessary temporal resolution for whole brain studies. The methods we are developing will be tested first in phantoms, and mathematical modeling will be developed to aid our understanding of the underlying physical principles behind susceptibility contrast. Quantitative evaluation of the relationship between MR signal changes and contrast agent concentration will be performed in vivo in normal animals over a range of flow states. These data will be correlated with quantitative radionuclide measurements of CBV and CBF. Animal models of altered cerebral physiology will then be studied, including ischemic disease with and without reperfusion, and tumor models with disruption of the blood-brain barrier (BBB). This will allow us to establish the capability of dynamic susceptibility contrast methods to extract quantitative information on regional CBV, CBF, and blood-brain barrier (BBB) permeability in diseased brain, and to motivate necessary refinements to our theoretical and empirical understanding of susceptibility contrast phenomena. MR techniques will then be applied in a pilot clinical study of patients with primary gliomas, for whom hemodynamic imaging offers important potential diagnostic and disease management advantages. PET imaging will be used as a gold standard for CBF, CBV, and glucose utilization in a subset of these patients. Functional MR images will be registered and quantitatively compared region by region with PET functional maps. This will allow us to ascertain the relationship between hemodynamic parameters, determined with our dynamic contrast techniques, and functional attributes in the brain. Finally, specific hypotheses related to tumor extent, response to treatment, and tumor recurrence will be tested in order to provide preliminary answers and the additional information needed to design definitive clinical trials.